Textured micro implants

ABSTRACT

An improved micro-implantation method and composition for filling depressed scars, unsymmetrical orbital floors, muscle, lip, and other soft tissue defects is provided for use in reconstructive surgery procedures. Textured micro particles having an outside diameter between about 30 microns and 3000 microns are used with an appropriate physiologic vehicle cannula and syringe and/or pressure delivery system into a predetermined locus. The particles provide long-term filling of defects without migration loss.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of application Ser. No. 08/052,414, filed Apr.22, 1993, abandoned, which is, in turn, a continuing application of Ser.No. 07/714,273, filed Jun. 12, 1991, now U.S. Pat. 5,258,028 issued Nov.2, 1993, which is a continuation-in-part of application Ser. No.07/282,671, filed Dec. 12, 1988, now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates generally to the field of surgery and moreparticularly to surgery directed to the repair of injuries or defects,usually considered plastic and reconstructive surgery of the human body.

In the practice of plastic and reconstructive surgery, it is oftennecessary to employ the use of tissue or foreign materials to provide ameans to fill in defects which may be present in the human body. Onesuch defect which occurs is enophthalmus wherein one eyeball cannot becoordinated with the other due to differences in the volume of theorbital contents which may have been created by either trauma ordevelopmental anomaly. Such a volume defect prevents coordination ofbinocular vision, interferes with appropriate opening and closing ofdefective eyelids, and adversely affects appearance.

Another exemplary defect is an uneven vermillion border that is theresult of a laceration, or from a cleft lip surgical repair. During theinitial opposition of the separated tissues, there is tension andresultant loss of three dimensional symmetry of structure. By increasingthe volume of the lip, three dimensional symmetry of structure isrestored and the vermillion border is not disrupted. Paralysis orablution of the vocal cords causing aphonia or dysphonia may becorrected by such augmentation. Traumatic or surgically altered bones,skin and subcutaneous tissue often have similar defects that interferewith form, function, or both.

In the practice of plastic and reconstructive surgery, inert materialshave frequently been implanted to fill these defects. Recently, variouscollagen compounds and fibrin matrices have been injected to fill thesedefects. Bioactive materials such as hydroxyapatite or cordal granules(osteo conductive) have been used for hard tissue defects. Another priorart technique is to use adjacent or distant autologous tissues. Also,but on a rare or infrequent basis, cadaver and other species tissueshave been used for fill-in substances. Liquid silicone has been used inthe past as an injectable substance for very small defects. Althoughsome scar tissue forms around the silicone liquid droplets, it issubject to rampant and distant migration throughout the body and theultimate location for such substances tends to be unpredictable. As aresult, liquid silicone has generally been viewed as a dangeroussubstance by most plastic surgeons. Although it has been useful incontrolled studies in very small (one-tenth of a cc. to 1 cc.)injections, it is currently not approved for general use because of itstendency to migrate.

While it has been suggested to compound certain very small particlespecies in a lubricious material and to inject such combination microparticle media subcutaneously for both soft and hard tissueaugmentation, heretofore success has been limited. Undesirablesubsequent particle migration and serious granulomatous reactionscommonly resulted. This is well documented with such materials aspolytetrafluoroethylene spheres of very small diameter (>90% of adiameter ≦30 microns) in glycerine. See, for example, Malizia, et al.,JAMA, Volume 251, No. 24, pp. 3277-3281 (1984), as a typical commentaryor evaluation. The use of very small diameter particulate spheres(approximately 1-20 microns) or small diameter elongated fibrils,(generally 1-30 microns in diameter) of various materials such ascross-linked collagen in a biocompatible fluid lubricant as injectableimplant compositions are disclosed in U.S. Pat. No. 4,803,075. Whilethese materials create immediate augmentation, they also have a tendencyto migrate and/or be reabsorbed from the injection site.

In accordance with the present invention, very small particles or microparticles and, in particular, textured micro particles are employed asan injectable solid substance for use in reconstructive surgicalprocedures. Textured micro particles having an outside diameter ofbetween about 30 and 3000 microns (or between approximately 0.003 and0.3 cm.) may be injected into the body along with an appropriatephysiologic vehicle to enable the filling of defects. Accordingly, andin accordance with the present invention, textured micro particles to bedescribed in more detail hereinafter may be employed which arefabricated from an elastomer such as silicone, an inert material such aspolytetrafluoroethylene (Teflon), bioactive materials such ashydroxyapatite, ceramics or other inert substances. These textured microparticles may be introduced and placed at a precise location, andbecause of the textured configuration, tissue ingrowth will preventdislodgement and ultimate migration. Furthermore, any over-correctioncan be readily adjusted by use of blunt cannulas and suction whichprovides for safe removal.

SUMMARY OF THE INVENTION

In accordance with the present invention, textured micro particleshaving a nominal diameter of between about 30 and 3000 microns (0.003 to3.0 mm) are selected. These textured micro particles present generallyamorphous surfaces, and normally possess indentations ranging in sizefrom, for example, 10Å (angstroms) to 500 microns with the indentationshaving irregular configurations and surfaces. Furthermore, a minimalinter-indentation distance is provided so that the particles may beinjected through an appropriate hypodermic needle of the appropriatepreselected size, and with or without an appropriate physiologicvehicle. Examples of appropriate physiologic vehicles are saline,various starches, hydrogels, polyvinylpyrrolidones, other polymericmaterials, polysaccharides, organic oils or fluids, all of which arewell known and utilized in the art. Vehicles that are biologicallycompatible, i.e., cause minimal tissue reaction and are removed ormetabolized without cytotoxicity, are, of course, utilized.

Biologically compatible saccharides such as glucose have been founduseful. Vehicles such as aqueous solutions of starch may also beemployed. In certain instances, it may be desirable to employ a totallyinert vehicle such as silicone oil or the like. Certain fats may also befound useful. In this connection, highly compatible vehicles includeesters of hyaluronic acids such as ethyl hyaluronate andpolyvinylpyrrolidone (PVP). PVP normally has the general empiricalformula [(CHCH₂)₂ N(CH₂)₃ CO]_(n) wherein n equal 25-500, a form ofwhich is otherwise known and marketed as Plasdone™ (trademark of GAFCorporation, New York, New York). Additionally, polyvinylpyrrolidone(Plasdones), hyaluronate, collagen and other biocompatible substancesmay be incorporated into the elastomer or combined with its surface.Another biocompatible vehicle is the patient's own plasma. Blood may bewithdrawn from the patient, centrifuged to remove cells (or not) andmixed with appropriate aliquots of particles and the mixture injected inthe desired locations.

It certain instances, it has been found desirable to utilize a surfacemodifier in combination with the micro particles, with materials such aspolyvinylpyrrolidone, collagen, or hyaluronates having been foundsuitable. A surface modifier may be defined generally as a materialcombined into the formed particle, applied to the surface of theparticle or added to the carrier vehicle to alter inter-particle orprosthesis-host interaction and/or particle identifiability. Thesesurface modifiers may alter the coefficient of friction of the particlesas by making them more lubricious, render the particles more radiopaque,assist in detoxification, and/or render the surface of the particlesmore susceptible to tissue ingrowth.

In this connection, the surface modifiers such as polyvinylpyrrolidoneor polytetrafluoroethylene may be mixed into the substance of or withthe micro particles, and furthermore may thereafter be coated with alayer of a hyaluronate or hyaluronic acid. Specifically, certainmodifiers such as polytetrafluoroethylene may be admixed with, forexample, a poly di-substituted siloxane particle material prior to cureto impart an average surface modification to the cured particle. Amaterial such as hyaluronic acid may be attached to the micro particlesurface either through physical or chemical bonding. Surface modifiersalso can be used to typically assist in detoxification and promote thedesired tissue ingrowth encapsulation. Other bioactive substances thatcan be included in the carrier or attached to the surface of the beadsto promote encapsulation include fibronectin, transforming growth factorbeta, and various other cytokines such as interleukin-1.

Once implanted, the body will form a thin scar tissue around each of theimplants so as to provide initial encapsulation. Polyvinylpyrrolidone,hyaluronate or collagen or other biocompatible substances may bechemically or physically combined with the particle substance or itssurface to enhance the acceptance of the implant by the host. While inmost situations the particles are of random size and configuration, butwithin the constraints of size indicated, it is generally desirable thatthe particles be of generally uniform configuration whenever possible.

For example, for soft tissue, a soft elastomer such as silicone rubberis a desirable material for the textured particles. When a firm area isbeing treated, such as connective tissue or the like,polytetrafluoroethylene (Teflon) or polyethylene may be satisfactorilyutilized. In those instances wherein the requirement is for hardsubstances, biocompatible materials such as certain calcium saltsincluding hydroxyapatite or other such crystalline materials,biocompatible ceramics, biocompatible metals such as certain stainlesssteel particles, or glass may be utilized.

By way of further background, the average diameter of a capillary isapproximately 16 microns, or roughly two times the diameter of a redcell. Therefore, since the size of the textured micro particles is inthe area of at least approximately 30 microns, they will not be absorbedinto the capillaries, but will on the other hand, remain generallycaptive and fixed in place. Smaller particles, in the sub-micron range,have been implicated in causing inflammation and may be ingested by hostcells. Thus, particles in the range of between about 30 and 3000 micronsare employed.

The fibroblast cell is the scar-forming cell of the human body, andthese cells range in size from between about 20 microns up to about 100microns, and because of contact guidance, it will form a scar tissue orcollagen-based coating around an inert foreign body. Furthermore, suchscar tissue will conform to the irregularities in the surface of theforeign body, particularly if they are of sufficient size to accommodatetissue ingrowth. Our previous studies (American Society of ArtificialInternal Organs; U. S. Pat. Nos. 3,638,649; 3,657,744; 4,239,492; and4,240,794) have shown that foreign substances can be substantiallyfirmly anchored in a predetermined location in the body. Because of theinherent ability of fibroblasts to form scar tissue in and aroundirregularities of the surface, such anchoring occurs in many locations,including locations within the blood stream.

Therefore, it is a primary object of the present invention to provide animproved method and apparatus for use in reconstructive surgicalprocedures, with the method employing textured micro particles which maybe injected along with an appropriate physiologic vehicle into apredetermined locus within the body.

It is yet a further object of the present invention to provide animproved method and apparatus for use in reconstructive surgicalprocedures wherein textured micro particles having an outside diameterof between about 30 and 3000 microns may be employed along with anappropriately selected physiologic vehicle for implantation or injectioninto a predetermined locus.

It is yet a further object of the present invention to provide animproved method and apparatus for use in reconstructive surgicalprocedures wherein textured micro particles having an outside diameterof between about 30 and 3000 microns may be injected into apredetermined locus of the body for the purpose of filling of defects inreconstructive surgery, with a syringe device having an inwardly taperedout-flow tract being desirable for use with particles having a sizewithin the upper range.

Other and further objects of the present invention will become apparentto those skilled in the art upon a study of the following specification,appended claims, and accompanying drawings.

IN THE DRAWINGS

FIG. 1 is a perspective view of a textured micro particle useful inaccordance with the present invention, and illustrating surfaceirregularities typically present in the particle;

FIG. 2 is a vertical sectional view taken along the line and in thedirection of the arrows 2--2 of FIG. 1;

FIG. 3 is a schematic illustration of a fragmentary portion of humanskin organ, and illustrating a hypodermic needle of appropriate sizebeing utilized to introduce materials in accordance with the presentinvention into the subcutaneous zone beneath a depressed scar;

FIG. 4 is a view similar to FIG. 3, and illustrating the same locationfollowing subcutaneous injection of the textured micro particles inaccordance with the present invention;

FIG. 5 is a perspective view of a modified form of useful particlewherein the surface irregularities project outwardly from a body memberin pillar form, with the central body portion being in the form of aspheroid; and

FIG. 6 is a cross-sectional view of the device of FIG. 5.

DESCRIPTION OF THE PREFERRED EMBODIMENT

With attention being directed to FIG. 1 of the drawings, it will beobserved that a micro-implant particle generally designated 10 comprisesan inner-core having randomly distributed throughout its surface,various surface irregularities indentations interstices, cavities,openings or pores 11--11. These pores referred to collectively as poresare spaced apart by connective pillar members 12. As indicated above,the pores preferably have a minimum indentation depth or open dimensionof about 10 Angstroms, along with a maximum dimension of about 500microns. The interconnective or pillar zones 12--12 which separate orotherwise define solid material between pores 11--11 have a dimension orbreadth sufficient so that the majority or greater portion of thesurface is defined by indentations, pores.

With continued attention being directed to FIGS. 1 and 2 of thedrawings, connective elements 12 are available on the surface of themicro-implant particles and provide for mechanical stability of theindividual particle. This arrangement is illustrated in particular inFIG. 2.

In accordance with the present invention, it has further been found thatinert foreign tissue augmentation particulate matter having a meandiameter less than about 30 microns will generally become subject tosignificant migratory loss from the site of injection regardless ofsurface configuration absent extraordinary protection. The texturednature of the surface of the microspheres of the invention, however,imparts to them an apparent size equivalency which, in the case of atleast the relatively smaller sized particles (particularly in the rangeof 30-60 and up to 80 microns), makes them behave, once injected, asmuch larger smoother particles might behave with respect to host implantor prosthesis migration tendencies and benign assimilation in scartissue. Particulate matter of the class of the present invention whichis of a preferred size ranging from about 30 microns to about 3000microns and having a textured surface in which the surfaceirregularities vary in size over a range of about 10 Angstroms to 500microns.

The irregularities, pores and interstices are designed to have widthsranging from those having a diameter or opening size which will justaccommodate the infiltration of a typical connective tissue fibril orprotein molecule at the lower end to those large enough to accommodateingrowth of much larger cross-linked protein, possibly collagen protein,fibrillar structures or actual fibroblasts at the high end. In thisregard, it is well known that the collagen fiber is composed of fibrilsand filaments. The basic poly-peptide chain is arranged intomicro-filaments of tropocollagen having a diameter of approximately 20Angstroms. It has been found that surface irregularities as small as 10Angstroms will interdigitate with the filaments on the surface of thefibers and serve to resist host-prosthesis interface motion.

Further, with respect to particle size, it will be appreciated thatparticle size, particularly of those species contained in preparationsutilized in prior injectable compositions, tends to vary over a rangewithin any group of particles so that there will be a percentage of thegroup larger and a percentage of the group smaller than at target sizein any such composition. In addition, the shape and size of the poresassociated with a given group of particles will also describe a range.It will further be appreciated that one must take into account thenormal variation in patient-to-patient acceptance and reaction to tissueaugmentation injection of micro particles. With this in mind, certainobservations have been made regarding optimum particle size,particularly with regard to the severe problems of unwanted migrationand formation of granulomatous reactions.

Observations in a variety of clinical situations indicate that particlesless than about 60 microns in diameter can be engulfed by macrophagesand transported to regional lymph nodes. Submicron-sized particles maybe the most easily transported and may remain intracellularindefinitely. However, larger particles, particles that approach thesize of a macrophage, i.e., from about 20 to about 60 microns, may causethe death of a cell when engulfed. This begins a progression in whichthe dead cell releases its intercellular enzymes (cytokines), and thoseattract other phagocytes which, again, encounter and engulf the particlewith the debris of the first encounter. In this manner, a vicious cyclecontinues on a larger scale as a chronic inflammatory response. 0fcourse, such a response is highly undesirable.

Particles greater than about 60 microns, however, have not been observedwithin a cell or within lymph nodes; and, certainly, particles greaterthan 80 microns appear safe from initiating such foreign body reactions.Further, as in the example below, particles of an average diameter of100 to 600 microns with textured surfaces having an average pore sizefrom about 10 microns to about 200 microns have been observed to workquite well. Theoretically, there is no upper limit to the size of thetextured particles, and this is borne out by the success ofsintered-surface hip implants, textured breast implants and others.However, the useful upper limit of micro implant dimensions is probablysomewhere in the vicinity of 1 to 3 mm in defects just beneath the skinsurface because particles of a size greater than this may be perceivedas surface irregularities when palpitated. Large textured implants havealso been employed in breast reconstruction, for example.

It will be appreciated that textured spheroids of the class contemplatedfor use in the present invention may be molded, for example, by anygravity-free technique wherein the spheroids are formed with centrifugalforce equal to that of gravity in cases where the spheroids are formedof rather malleable synthetic material. Spheroids can be fabricated froma variety of inert substances such as polytetrafluoroethylene,poly(methyl-methacrylate), poly substituted siloxanes (silicones) and avariety of other synthetic polymeric materials, ceramics and others anddifferent fabrication processes may be applicable to each material forthe augmentation of soft tissue. Of course, fabrication of the spheroidsfrom a malleable polymer material such as a silicone rubber is preferredas it will more closely imitate the texture of the natural tissue itreplaces. With respect to malleable polymers such as silicone rubber,the following fabrication techniques are exemplary of those that willreadily enable manufacture by those skilled in the art. It will beappreciated that a technique that might be preferred for one materialmay not work equally well for all.

In one process, a malleable stock of unvulcanized polydimethylsiloxaneis rolled into spheroids of approximately 100 microns or other desiredsize diameter. The surface is then textured by impacting each spheroidwith an appropriate force. The textured spheroids are then vulcanizedand mixed with the appropriate vehicle for injection.

In another successful method, generally preferred for forming beads ofsilicone rubbers, poly(di-substituted siloxane) silicone rubber of thetype desired, normally poly(dimethyl siloxane) may be dispersed in anappropriate volatile solvent and then partially cured by droplets beingforced through a specific distance of air from an orifice having aspecific diameter. This is a very familiar process technique generallyknown with respect to the operation of a shot tower in making lead shot.The size of the beads or spheroids is easily regulated by varying theviscosity of the mixture and/or the orifice of origin. As the particletravels a known distance through air, it is partially cured as thevolatile vehicle evaporates. The specifically formed spheroid or bead isthen separated by a suitable fluid medium. The spheroids may then bepressed against an appropriate surface or impacted by an appropriateforce to impart the desired texture, the surface having an appropriatemold release. Partially cured spheroids are then vulcanized by heatirradiation. The particles are then sized and graded by physical means.Spheroids are then mixed with the appropriate vehicle in appropriateratios, placed in containers and finally sterilized within thecontainer.

Texture can be imparted to the beads or spheroids in a number of ways.In addition to the molding method, other techniques include ion-beammicrotexturing which makes it possible to produce controlledmicrotextured surfaces, chemical and plasma etching and impacting thebeads with solid particles. Of course, it is contemplated that othermethods could also occur to those skilled in the art.

If desired, surface modifiers, as explained above, can be incorporatedin the material prior to formation of the spheroids or beads or may bethereafter be added as a coating on the deformed surfaces. In thismanner, certain materials such as hyaluronic acid, for example, may beattached to the micro particle surface either through physical orchemical bonding in a well-known manner after formation and texturing.

EXAMPLE I

Amounts of particles with average diameters of 100, 150 and 600micrometers were fabricated with a textured surface from fullypolymerized and vulcanized poly(dimethylsiloxane). The polymer was mixedto form a biocompatible solution with an organic polymer hydrogel. Thehydrogel was a polyvinylpyrrolidone gel having an average molecularweight of approximately 13,700 and one of a family of such materialknown as Plasdones. These materials in the molecular weight range ofinterest are freely transported through tissue fluids and excretedunchanged by the kidneys. The mixture utilized was approximately 38% byweight of the polymer and 62% of the gel material. The polymer/gelmixture was diluted with deionized water, mixed until the inertparticles were evenly dispersed and then placed in 1-cc cylinders withsmall pistons placed in the proximal ends. The distal end of eachcylinder would be attached to a 1-cc syringe with a Luer lock on the endand a piston member could be inserted in the proximal barrel. A highlyleveraged injection ratchet mechanism was utilized to accept the syringecartridges and deliver precise amounts of the gel mixture through acannula into the subcutaneous plane of the ear tissue of 20 large, adultwhite rabbits. Controls using commercially available collagenderivatives were injected in the subcutaneous plane in adjacent sites inthe rabbits'ears using small gauge needles provided by the manufacturersof the collagen derivatives.

With respect to the injected collagen control sites, subsequenthistologic sections indicated that after three weeks, no residualcollagen could be found at the site of the injection. In dramaticcontrast, the histologic sections of the micro particles evidenced adramatic transition in which the gel phase of the material was replacedby a fibrin and protocollagen matrix surrounding each of the microparticles. In three days, the fibrin matrix was complete, with all thegel having been removed by the host. Connective-tissue cells haddeveloped and had begun to replace the matrix with host collagenfibrils. By the sixth week, this fibrosis was complete, and eachindividual textured particle appeared to be encased in its ownindividual inner connected covering of fibrous tissue. The thickness ofthe implanted area and the degree of fibrosis as measured bytransillumination, micrometer and light and electron beam microscopyremained constant for more than a year.

Subsequent histologic examination of the regional lymph nodes at thebase of the rabbit ears revealed no migration of particles.Cross-sections of the ear below the injected area showed no particles.Through transillumination, the size and density of the areas ofinjection were easily and atraumatically monitored for each rabbit. Notextured micro implants were found at the base of the ears or in theregional lymph nodes of any of the rabbits under study.

The dimensions of the subcutaneous deposits of textured micro implantsremained approximately the same throughout the period of study, as wasevidenced by transillumination photographic record and micrometermeasurement. Opacity was noted to decrease over the last few weeks asthe transillumination became brighter but then appeared to stabilizebetween the end of the first and the sixth months.

The results obtained with the experimental particles of Example 1illustrate the dramatic contrast between this material and the injectionof collagen-containing materials. Although the collagen-containingmaterials created immediate soft tissue augmentation, thesesubstances--which are only about 3.5 to 6.5% solid collagenmaterial--soon became invaded by host capillaries and were absorbed. Noabsorption or migration of the 100, 150 or 600 micron silicone rubberparticles was observed, even after 382 days.

In other experiments, particles having an average diameter of 80 micronsand incorporating tracer material in the form of gammaradiation-emitting material were injected into the ears of otherrabbits. These particles showed no migration from the injection siteduring a subsequent six-month monitoring period.

While prior work by the inventors and others have shown that surfaceirregularities preferably are in the 20 to 200 micron range in order toachieve adequate contact guidance of the fibroblasts so as to create ordevelop a scar tissue pattern that is a mirror image of the substratesurface, it is also appreciated that the particle size in relation tothe relative size of the surface irregularities is a factor to beconsidered. In this connection, if the openings, pores are too shallowin their depth dimension, or in the event their diameter is notsufficiently great, the fibroblasts will tend to bridge across thedefect so as to provide a substantially smooth surface. In the preferredembodiment of the present invention, the particles indicated or selectedfor a specific procedure to assist in correcting a given defect arepreviously loaded into a hypodermic syringe with a needle having anadequately sized interior bore so that upon injection of the needle intothe area of the depression being corrected, the particles together withthe appropriate physiologic vehicle enables the spheroids to be injecteddirectly into the area of the depression. Appropriate vehicles, aspreviously indicated, include physiologic saline or polysaccharidelubricants, each of these enabling the spheroids to be injected as setforth.

With attention being directed to FIG. 3 of the drawings, it will benoted that surface tissue as shown at 20 includes a depression area 21,with the depression area extending into the subcutaneous tissue as at22. For utilization of the concept of the present invention, the needle23 is shown as it is injected into tissue. Particles 30, of the typeillustrated in FIGS. 1 and 2, along with vehicle 31 are injected intothe predetermined site, with the result being filling of the depressionarea, particularly as illustrated in FIG. 4. Upon withdrawal of theneedle 23, the injected material is left in situ at the selected site.The supply of particles 30 retained and carried within vehicle 31 may beconveniently retained in syringe body zone 23A for passage throughhollow needle 23. Syringes of this type are, of course, commerciallyavailable, and suitable for particles in the low to mid-size range,while larger particles within the size range may require an inwardlytapered out-flow tract. For certain applications, it has been founddesirable to utilize a syringe-needle combination which taperscontinuously, thereby providing an elongated syringe-needle combinationwith a inwardly tapered out-flow tract.

Generally, upon completion of the inflammatory phase of wound healing,or after approximately one week, formation of scar tissue commences withthis becoming complete after about three weeks. Following completion ofthe deposition and formation of scar tissue, a remodeling phase oroperation may be undertaken. In view of the specific irregularities andindentations of the surfaces of the individual particles, contactguidance will normally allow for the resulting scar tissue to firmlyanchor and attach the implanted particles 30 wherever deposited. Asborne out by the example, although various biological substances havebeen used for similar purposes, such as collagen and fibril, these otherpreviously utilized substances are normally broken down by the body overa period of time and digested autogenously. It is anticipated that themicro particles fabricated of silicone rubber, polytetrafluoroethylene(Teflon), ceramic or other appropriate inert substances will mimic thedurometer hardness of the host tissue being filled, with the softermaterials, such as silicone rubber being utilized for normalsubcutaneous fat tissue, and with ceramic materials being utilized forbone tissue. Polytetrafluoroethylene (Teflon) is deemed suitable forcartilage, and silicone elastomer with variations in firmness forsubcutaneous fat in various regions of the body. In the event theprocedure involves an over-correction, the use of lipoplasty techniquesof suction lipectomy with a cannula of appropriate diameter will allowfor fine tuning, even after several months or years. Removal of anappropriate quantity of filler material may be accomplished in thatfashion.

Specific attention is now directed to the modification of particleconfiguration illustrated in FIGS. 5 and 6. Specifically, the texturedmicro particle generally designated 40 comprises a central body portion41 of generally spheroidal form, together with a number of outwardlyprojecting pillar members 42--42 thereon. Inter-pillar indentations ofgenerally arcuate form are shown at 43--43. Textured micro particles ofthe type illustrated in FIGS. 5 and 6 may also be found useful inconnection with the various aspects of the present invention. In actualuse, these micro particles will be combined with an appropriate vehicle,of the type previously referred to, such as physiologic saline, PVP orpolysaccharide lubricant, so as to enable these textured micro particlesto be injected into the body. Also, textured micro particles of the typeillustrated in FIGS. 5 and 6 may be formed of the same material asindicated in connection with the embodiment of FIGS. 1-4, such as forexample, silicone rubber, polytetrafluoroethylene (Teflon),biocompatible solids such as, for example, hydroxyapatite or otherbiocompatible solids of the type listed hereinabove.

Radiopaque substances may be utilized, such as, for example, bariumcompounds to make the particles more visible. Radioactive materials mayalso be incorporated for certain applications. In most instances,however, utilization of such radiographic tagging will not be required.

It will be appreciated that the specific examples provided herein aregiven for purposes of illustration only, and are not to be construed asa limitation upon the scope of the present invention, and that thoseskilled in the art may depart from the specific examples withoutactually departing from the spirit and scope of the present invention.

What is claimed is:
 1. An injectable particulate implantation system forlong-term augmentation of soft tissue, comprising in combination:(a) anamount of generally soft, malleable, elastic, biologically compatiblenon-resorbin prosthetic particles dispersed in a non-retentivecompatible physiological vehicle, said particles being furthercharacterized by a rough surface texture having a plurality of surfaceirregularities generally randomly formed therein; (b) said implantationsystem incorporating a combination of average particle size and averageparticle texture sufficient to cooperate in an autogenous manner tosubstantially prevent loss of said particles from an augmentation site,said particles remaining in situ to form part of a permanent implant. 2.The injectable implantation system of claim 1 being particularlycharacterized in that the range of average particle size is between 100microns to 600 microns.
 3. An injectable particulate implantation systemfor long-term augmentation of soft tissue, comprising in combination:(a)biologically compatible particles of a relatively soft, resilient,non-resorbing material dispersed in a non-retentive compatiblephysiological vehicle, the particles being further characterized by arough surface having a plurality of surfaces irregularities randomlyformed therein and further comprising openings or pores; (b) theparticles having an average particle size generally between 30 and 3000microns with a dimension of the openings formed by the pores within theparticles being generally in a range between 10 angstroms and 500microns; (c) wherein the implantation system average particle size andaverage roughness of texture are sufficient in combination to, in anautogenous manner, substantially preclude migration of the particlesfrom an augmentation site, such that the particles remain in situ toform part of a permanent implant.
 4. The injectable implantation systemof claim 3 wherein the particles further comprise an amount of at leastone surface modifier to accomplish at least one of assisting indetoxification and promoting tissue ingrowth.
 5. The injectableimplantation system of claim 4 wherein the at least one surface modifieris incorporated into the micro particle prior to particle formation. 6.The injectable implantation system of claim 4 wherein the at least onesurface modifier is selected from the group consisting of polyvinylpyrrolidone, collagen and an hyaluronate.
 7. The injectable implantationsystem of claim 6 wherein the surface modifier is dispersed in thephysiological vehicle.
 8. The injectable implantation system of claim 7wherein the surface modifier is biologically active.
 9. The injectableimplantation system of claim 4 wherein the surface modifier isbiologically active.
 10. The injectable implantation system of claim 4wherein the modifier is selected from the group consisting offibronectin and cytokines.
 11. The injectable implantation system ofclaim 3 being particularly characterized in that the compatiblephysiological vehicle is a bodily compatible fluid selected from thegroup consisting of hydrogels, glucose, starch, silicone fluid, lipidand a hyaluronate.
 12. The injectable implantation system of claim 3being particularly characterized in that the biologically inertparticles are formed of bodily compatible solids selected from the groupconsisting of silicone rubbers, polytetrafluoroethylene, polyethylene,and other biologically inert polymer materials.
 13. The injectableimplantation system of claim 12 being particularly characterized in thatthe average particle size is at least 60 microns.
 14. The injectableimplantation system of claim 13 further characterized by micro particleshaving a textured surface of pores of an average size between about 10microns and about 200 microns.
 15. The injectable implantation system ofclaim 12 being particularly characterized in that the range of averageparticle size is between 100 microns to 600 microns.
 16. The injectableimplantation system of claim 3 being particularly characterized in thatthe average particle size is at least 60 microns.
 17. The injectableimplantation system of claim 16 being particularly characterized in thatthe biologically inert micro particles are of a generally uniformconfiguration.
 18. The injectable implantation system of claim 3 beingparticularly characterized in that the range of average particle size isbetween 100 microns to 600 microns.
 19. A non-migratory injectableparticulate implantation system for long-term augmentation of softtissue, comprising in combination:(a) generally soft, resilientbiologically inert, micro particles of a material of a material notresorbed by the body dispersed in a non-retentive compatiblephysiological vehicle, the micro particles being further characterizedby a surface texture having a plurality of surface irregularitiesgenerally randomly formed therein; (b) said implantation system having,in combination, an average particle size range and average particletexture such that migration from an injection site is substantiallyprecluded in an autogenous manner and individual particle non-chronicinflammatory scar tissue encapsulation occurs, said particles therebyremaining in situ to form part of said implantation system.
 20. Aninjectable particulate implantation system for long-term augmentation ofsoft tissue, comprising in combination:(a) generally soft, resilientbiologically inert nonresorbing implant particles having a generallyrough surface dispersed in a non-retentive compatible physiologicalvehicle, the micro particles being of a generally uniform configurationand being further characterized by a surface texture having a pluralityof surface irregularities separated by connective members generallyrandomly formed therein; (b) the textured particles being formed ofmaterials selected from the group consisting of silicone rubbers,polytetrafluoroethylene, polyethylene, and other biologically inertpolymer materials, and having an average particle size generally between60 and 3000 microns with dimensions of surface irregularities within theparticles being generally in a range between 10 angstroms and 500microns; and (c) said implantation system incorporating an averageparticle size and average texture roughness to, in combination in anautogenous manner, substantially preclude migration of said particlesfrom an injection site and achieve adequate guidance of fibroblasts suchthat a scar tissue pattern is developed that assumes a configurationthat is generally in accordance with adjacent particle surfaces, saidparticles thereby remaining in situ to form a permanent part of saidimplantation system.